Efficacy of A Mouse Anti-human ICAM-1 Monoclonal Antibody, MD-3, for Kidney Transplantation in Rhesus Monkeys

Abstract

Introduction: The MD-3 is a newly developed chimeric anti-human intracellular adhesion molecule 1 (ICAM-1) monoclonal antibody (mAb). The effects of this monoclonal antibody in solid organ transplantation have not been elucidated. Methods: Five rhesus monkey renal allograft recipients treated with MD-3 induction and one recipient without MD-3 treatment were studied for the incidence of acute rejection and donor-specific antibody development. Cellular immune response was tested with ELISPOT assay. Development of anti-drug antibody was also tested. Maintenance immunosuppression included anti-CD154 mAb (hu5C8), mycophenolate mofetil and corticosteroid. Results: No recipient monkey developed acute rejection as long as 8 months after transplantation. Donor-specific antibody was not developed in monkeys treated with MD-3. A monkey without MD-3 induction started to produce donor-specific antibody 3 weeks after cessation of anti-CD154mAb and persisted. No anti-drug antibody was detected during the study period. Conclusions: MD-3 can be a highly promising agent for clinical use in human allotransplantation and MD-3 treatment can allow optimization of kidney transplant outcome. Further studies for refining dosages and dosing schedule of MD-3 in kidney transplantation are required.